Project Summary Manganese (Mn) is an essential element, yet is neurotoxic in excess. Despite the fact that infants and young children may be at greater risk for Mn neurotoxicity than adults, very few studies have evaluated the effect of chronic Mn exposure on child development. Marietta, Ohio, a rural Appalachian community, has been home to the only metal refinery in the US and Canada for over 50 years. In response, the community formed Neighbors for Clean Air (NCA). The University of Cincinnati (UC) has been asked by NCA to assist them in understanding their exposure and related health effects, if any. For this project, Marietta Community Actively Researching Exposure Study (CARES), the community has defined the research agenda, determining the research questions, objectives, specific aims and identifying resources available within the community to conduct the research. Members of the community will be engaged in all facets of the research project, including environmental sampling, neurobehavioral assessment, project coordination, and collection of biological specimens. The primary objectives of this application are to examine biological indicators of Mn exposure in children and understand the effects of chronic manganese exposure in children. UC will provide training, oversight and expertise in environmental health research, to address the following hypothesis: Exposure to Mn during early childhood is significantly associated with neurodevelopmental deficits in high exposed children ages 7-8 years compared to an age matched low/unexposed group. In order to test the hypothesis, the following community-driven specific aims will be accomplished. Specific Aim 1: Assess environmental Mn exposure within a high Mn exposure community, Marietta, OH and a low Mn exposure community, Cambridge, Ohio. Specific Aim 2: Evaluate comparisons of the neurobehavioral effects in children exposed to Mn in a high Mn exposure community, Marietta, OH and a low Mn exposure community, Cambridge, Ohio. Specific Aim 3: Evaluate comparisons of the neuromotor effects in children exposed to Mn exposure community, Marietta, OH and a low Mn exposure community, Cambridge, Ohio. Given the unique susceptibility of children to toxicant exposure and the opportunity to study Mn exposure in a chronically exposed community, we anticipate this project to significantly impact local and national public health policy related to Mn exposure. Project Narrative Exposure to manganese (Mn) can result in neurological deficiencies, and here is great potential for global exposure to Mn in the form of MMT, an anti-knock agent to replace lead in gasoline. The Marietta Community Actively Researching Exposure Study (CARES) is a community-based study designed to explore the health effects of long term Mn exposure in children.